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Prostanoid production and pulmonary arterial responses to reactive oxygen species (ROS) are altered in newborn piglets with chronic hypoxia‐induced pulmonary hypertension
Author(s) -
Fike Candice Denise,
Kaplowitz M R,
Zhang Yongmei,
Pfister S L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a401-a
Subject(s) - prostacyclin , prostanoid , pulmonary hypertension , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , reactive oxygen species , thromboxane , thromboxane b2 , medicine , endocrinology , xanthine oxidase , vascular resistance , chemistry , prostaglandin , oxygen , platelet , biochemistry , blood pressure , enzyme , organic chemistry
Altered vascular responses to ROS could contribute to the development of chronic hypoxia‐induced pulmonary hypertension. ROS might mediate vascular responses, at least in part, by stimulating prostanoid production. Our goal was to determine if the effect of ROS on vascular tone and prostanoid production is altered in resistance pulmonary arteries (RPAs) of newborn piglets with chronic hypoxia induced pulmonary hypertension. Newborn pigs were kept in room air (C, n=7) or 11% O 2 (H, n=7) for 3 days. We exposed RPAs from C and H piglets to xanthine (X) plus xanthine oxidase (XO) and measured changes in vessel diameter and the production of 6‐keto‐prostaglandin F 1α (PGF 1α ) and thromboxane B 2 (TXB 2 ), the stable metabolites of the prostanoids, prostacyclin and thromboxane, respectively. In the presence of ROS derived from X+XO, RPAs from C piglets dilated slightly, by 5±5%, and production of both TXB 2 and PGF 1α increased by similar amounts, 30–40%. In contrast, in the presence of ROS derived from X+XO, RPAs from H piglets constricted by 30±5%; TXB 2 production doubled but PGF 1α production did not change. Thus, the response to ROS is altered from dilation to constriction and is accompanied by enhanced TXB 2 production in RPAs of H piglets. ROS could contribute to chronic hypoxia‐induced pulmonary hypertension by shifting the balance of prostanoids away from dilators, such as prostacyclin, towards constrictors, such as thromboxane, and thereby enhancing vasoconstriction. Supported by HL68572